N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation.

BACKGROUND: Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. METHODS: Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. RESULTS: circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. CONCLUSIONS: Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.

Nomogram prediction of the 70-gene signature (MammaPrint) binary and quartile categorized risk using medical history, imaging features and clinicopathological data among Chinese breast cancer patients.

BACKGROUND: The 70-gene signature (70-GS, MammaPrint) test has been recommended by the main guidelines to evaluate prognosis and chemotherapy benefit of hormonal receptor positive human epidermal receptor 2 negative (HR + /Her2-) early breast cancer (BC). However, this expensive assay is not always accessible and affordable worldwide. Based on our previous study, we established nomogram models to predict the binary and quartile categorized risk of 70-GS. METHODS: We retrospectively analyzed a consecutive cohort of 150 female patients with HR + /Her2- BC and eligible 70-GS test. Comparison of 40 parameters including the patients' medical history risk factors, imaging features and clinicopathological characteristics was performed between patients with high risk (N = 62) and low risk (N = 88) of 70-GS test, whereas risk calculations from established models including Clinical Treatment Score Post-5 years (CTS5), Immunohistochemistry 3 (IHC3) and Nottingham Prognostic Index (NPI) were also compared between high vs low binary risk of 70-GS and among ultra-high (N = 12), high (N = 50), low (N = 65) and ultra-low (N = 23) quartile categorized risk of 70-GS. The data of 150 patients were randomly split by 4:1 ratio with training set of 120 patients and testing set 30 patients. Univariate analyses and multivariate logistic regression were performed to establish the two nomogram models to predict the the binary and quartile categorized risk of 70-GS. RESULTS: Compared to 70-GS low-risk patients, the high-risk patients had significantly less cardiovascular co-morbidity (p = 0.034), more grade 3 BC (p = 0.006), lower progesterone receptor (PR) positive percentage (p = 0.007), more Ki67 high BC (≥ 20%, p < 0.001) and no significant differences in all the imaging parameters of ultrasound and mammogram. The IHC3 risk and the NPI calculated score significantly correlated with both the binary and quartile categorized 70-GS risk classifications (both p < 0.001). The area under curve (AUC) of receiver-operating curve (ROC) of nomogram for binary risk prediction were 0.826 (C-index 0.903, 0.799-1.000) for training and 0.737 (C-index 0.785, 0.700-0.870) for validation dataset respectively. The AUC of ROC of nomogram for quartile risk prediction was 0.870 (C-index 0.854, 0.746-0.962) for training and 0.592 (C-index 0.769, 0.703-0.835) for testing set. The prediction accuracy of the nomogram for quartile categorized risk groups were 55.0% (likelihood ratio tests, p < 0.001) and 53.3% (p = 0.04) for training and validation, which more than double the baseline probability of 25%. CONCLUSIONS: To our knowledge, we are the first to establish easy-to-use nomograms to predict the individualized binary (high vs low) and the quartile categorized (ultra-high, high, low and ultra-low) risk classification of 70-GS test with fair performance, which might provide information for treatment choice for those who have no access to the 70-GS testing.

A pH-Controlled Solid Inhibitor Based on PAM Hydrogel for Steel Corrosion Protection in Wide Range pH NaCl Medium.

To provide carbon steel a long-term corrosion protection effect in NaCl solutions with different pH values, based on poly-acrylamide (PAM) and oleate imidazoline (OIM), a solid corrosion inhibitor with the properties of pH-controlled release was synthesized. SEM, FTIR and TGA results indicated that the OIM inhibitors were successfully loaded into PAM hydrogel with a high OIM encapsulation content (39.64 wt.%). The OIM release behavior from the hydrogel structure has two stages, quick release and sustained release. The pH of solutions could affect the initial release kinetics of OIM inhibitors and the diffusion path in the hydrogel structure. Weight loss measurement of L80 steel in different pH solutions with OIM@PAM proved the inhibitor responsive release mechanism and anticorrosion performance. The inhibition efficiency of OIM@PAM can maintain over 80% after long-term immersion in a harsh corrosive environment (pH 3), which is much higher than the inhibition efficiency of OIM@PAM in a moderate corrosive solution.

Prognostic significance of different molecular typing methods and immune status based on RNA sequencing in HR-positive and HER2-negative early-stage breast cancer.

BACKGROUND: This study was conducted to evaluate the prognostic significance of different molecular typing methods and immune status based on RNA sequencing (RNA-seq) in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HR + /HER2-) early-stage breast cancer and develop a modified immunohistochemistry (IHC)-based surrogate for intrinsic subtype analysis. METHODS: The gene expression profiles of samples from 87 HR + /HER2- early-stage breast cancer patients were evaluated using the RNA-seq of Oncotype Dx recurrence score (RS), PAM50 risk of recurrence (ROR), and immune score. Intrinsic tumor subtypes were determined using both PAM50- and IHC-based detection of estrogen receptor, progesterone receptor, Ki-67, epidermal growth factor receptor, and cytokeratins 14 and 5/6. Prognostic variables were analyzed through Cox regression analysis of disease-free survival (DFS) and distant metastasis-free survival (DMFS). RESULTS: Survival analysis showed that ROR better predicted recurrence and distant metastasis compared to RS (for DFS: ROR, P = 0.000; RS, P = 0.027; for DMFS, ROR, P = 0.047; RS, P = 0.621). Patients with HR + /HER2- early-stage breast cancer was classified into the luminal A, luminal B, HER2-enriched, and basal-like subtypes by PAM50. Basal-like subgroups showed the shortest DFS and DMFS. A modified IHC-based surrogate for intrinsic subtype analysis improved the concordance with PAM50 from 66.7% to 73.6%, particularly for basal-like subtype identification. High level of TILs and high expression of immune genes predicted poor prognosis. Multi-factor Cox analysis showed that IHC-based basal-like markers were the only independent factors affecting DMFS. CONCLUSIONS: Prognosis is better evaluated by PAM50 ROR in early-stage HR + /HER2- breast cancer and significantly differs among intrinsic subtypes. The modified IHC-based subtype can improve the basal-like subtype identification of PAM50. High immunity status and IHC-based basal-like markers are negative prognostic factors.

Rationale and design of a phase II trial of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for N0/N1mi, HER2 + early breast cancer (PHAEDRA).

BACKGROUND: The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated. METHODS: This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1-7, then 4 mg bid on days 8-21) or the first 2 cycles (4 mg tid on days 1-7, then 4 mg bid on days 8-42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea. DISCUSSION: This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020.

HN1 promotes tumor associated lymphangiogenesis and lymph node metastasis via NF-κB signaling activation in cervical carcinoma.

Lymph node metastasis (LNM) is a critical cause for disease progression and treatment failure in cervical cancer. However, the mechanism underlying cervical cancer LNM remains unclear. In this study, HN1 was found to be dramatically upregulated in cervical cancer and patients with higher HN1 expression are more likely to exhibit a higher rate of LNM and lower survival rate. Univariate and multivariate Cox-regression analyses showed that HN1 is an independent prognostic factor in cervical cancer. Meanwhile, HN1 promotes lymphangiogenesis of cervical cancer in vitro. The in vivo experiment also indicates that HN1 enhances LNM in cervical cancer. Furthermore, we also found that HN1 activated the NF-κB signaling pathway to enhance the expression of downstream genes. Taken together, our study suggests that HN1 plays a crucial role in promoting LNM and acts as a prognostic biomarker in cervical cancer.

Three-Dimensional Ameliorated Biologics Elicit Thymic Renewal in Tumor-Bearing Hosts.

Cancer-initiating/sustaining stem cell subsets (CSCs) have the potential to regenerate cancer cell populations and are resistant to routine therapeutic strategies, thus attracting much attention in anticancer research. In this study, an innovative framework of endogenous microenvironment-renewal for addressing such a dilemma has been just developed. CSCs in three-dimensional multipotent spheroid-engineered biologics were prepared with 150 Gy radiation and inoculated into 15-mo-old BALB/c and C57BL/6 mice bearing diverse advanced tumors covering Mammary 4T1, liver Hepa, lung LL/2, and colon C26 tumors and distant metastases. Subsequently, the systematic microenvironment of tumor-bearing hosts was rapidly remodeled to resettle thymic cortex and medulla rudiment as an endogenous foxn1-thymosin reprogramming TCR-repertoire for resetting MHC-unrestricted multifunction renewal. Postrenewal Vγ4γδT-subsets would bind and lead migrating CSCs into apoptosis. Moreover, TCR repertoire multifunction renewal could reverse tumor metastases from tumoricidal resistance into eventual regression as a blockade of cancer-sustaining Bmi-1/Nanog-Oct4-Sox2 renewal loop with sequent multivalent depletion of both migrating/in situ CSCs and non-stem terminal cancer cell subsets. This study represents a promising start to set up a generalizable strategy of three-dimensional biologics evoking an endogenous integral microenvironment into pluripotent renewal versus advanced cancer.

Nuclear orphan receptor NR2F6 confers cisplatin resistance in epithelial ovarian cancer cells by activating the Notch3 signaling pathway.

The primary challenge facing treatment of epithelial ovarian cancer (EOC) is the high frequency of chemoresistance, which severely impairs the quality of life and survival of patients with EOC. Our study aims to investigate the mechanisms by which upregulation of NR2F6 induces chemoresistance in EOC. The biological roles of NR2F6 in EOC chemoresistance were explored in vitro by Sphere, MTT and AnnexinV/PI assay, and in vivo using an ovarian cancer orthotopic transplantation model. Bioinformatics analysis, luciferase assay, CHIP and IP assays were performed to identify the mechanisms by which NR2F6 promotes chemoresistance in EOC. The expression of NR2F6 was significantly upregulated in chemoresistant EOC tissue, and NR2F6 expression was correlated with poorer overall survival. Moreover, overexpression of NR2F6 promotes the EOC cancer stem cell phenotype; conversely, knockdown of NR2F6 represses the EOC cancer stem cell phenotype and sensitizes EOC to cisplatin in vitro and in vivo. Our results further demonstrate that NR2F6 sustains activated Notch3 signaling, resulting in chemoresistance in EOC cells. Notably, NR2F6 acts as an informative biomarker to identify the population of EOC patients who are likely to experience a favorable objective response to gamma-secretase inhibitors (GSI), which inhibit Notch signaling. Therefore, concurrent inhibition of NR2F6 and treatment with GSI and cisplatin-based chemotherapy may be a novel therapeutic approach for NR2F6-overexpressing EOC. In summary, we have, for the first time, identified an important role for NR2F6 in EOC cisplatin resistance. Our study suggests that GSI may serve as a potential targeted treatment for patients with NR2F6-overexpressing EOC.

Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study.

BACKGROUND: Anti-angiogenic therapy combined with chemotherapy could improve the outcomes of patients with platinum-resistant ovarian cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits VEGF receptor 2. We assessed the efficacy and safety of the combination therapy of apatinib and oral etoposide, considering the potential advantage of home administration without hospital admission, in patients with platinum-resistant or platinum-refractory ovarian cancer. METHODS: In this phase 2, single-arm, prospective study, we recruited patients aged 18-70 years with platinum-resistant or platinum-refractory ovarian cancer at the Sun Yat-sen University Cancer Center (China). The treatment consisted of apatinib at an initial dose of 500 mg once daily on a continuous basis, and oral etoposide at a dose of 50 mg once daily on days 1-14 of a 21-day cycle. Oral etoposide was administered for a maximum of six cycles. Treatment was continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoint was the proportion of patients achieving an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1. We used Simon's two-stage design, and analysed efficacy in the intention-to-treat and per-protocol populations. Safety analyses included enrolled patients who had received at least one dose of study medication, but excluded those without any safety data. This study is registered with ClinicalTrials.gov, number NCT02867956. FINDINGS: Between Aug 10, 2016, and Nov 9, 2017, we screened 38 and enrolled 35 patients. At the data cutoff date (Dec 31, 2017), 20 (57%) patients had discontinued the study, and 15 (43%) patients remained on treatment. Objective responses were achieved in 19 (54%; 95% CI 36·6-71·2) of 35 patients in the intention-to-treat population and in 19 (61%; 42·2-78·2) of 31 patients in the per-protocol population. The most common grade 3 or 4 adverse events were neutropenia (17 [50%]), fatigue (11 [32%]), anaemia (ten [29%]), and mucositis (eight [24%]). Serious adverse events were reported in two patients who were admitted to hospital (one patient had anaemia and anorexia; the other patient had increased ascites due to disease progression). No treatment-related deaths were recorded. INTERPRETATION: The combination of apatinib with oral etoposide shows promising efficacy and manageable toxicities in patients with platinum-resistant or platinum-refractory ovarian cancer, and further study in phase 3 trials is warranted. FUNDING: None.

LncRNA-FENDRR mediates VEGFA to promote the apoptosis of brain microvascular endothelial cells via regulating miR-126 in mice with hypertensive intracerebral hemorrhage.

BACKGROUND: LncRNA-FENDRR is a kind of endothelial genes critical for vascular development. Moreover, miR-126 and vascular endothelial growth factor A (VEGFA) are also involved in the physiological process of vascular endothelial cells. This study aimed to the underlying mechanism of FENDRR involving miR-126 and VEGFA in hypertensive intracerebral hemorrhage (HICH). METHODS: C57BL/6 mice were chosen to establish HICH model. The expression of FENDRR, miR-126, and VEGFA at mRNA level was determined by qRT-PCR. The protein expression of VEGFA was assessed using Western blot. RIP assay and RNA pull-down assay were used to the relationship between FENDRR and miR-126. Flow cytometry was used to analyze cell apoptosis. RESULTS: The levels of FENDRR and VEGFA were increased, and miR-126 expression was decreased in vascular endothelial cells (VECs) from the right brain of model mice and human brain microvascular endothelial cells (HBMECs) treated by thrombin. Overexpression of FENDRR promoted the apoptosis of HBMECs. FENDRR regulating VEGFA participated in HBMECs apoptosis through targeting miR-126. Downregulation of FENDRR was indicated to relieve the HICH in mice. CONCLUSIONS: FENDRR could promote the apoptosis of HBMECs via miR-126 regulating VEGFA in HICH.

Stonin 2 Overexpression is Correlated with Unfavorable Prognosis and Tumor Invasion in Epithelial Ovarian Cancer.

Stonin 2 (STON2), which functions in adjusting endocytotic complexes, is probably involved in the monitoring of the internalization of dopamine D2 receptors which have an inhibitory action of dopamine on tumor progression. However, its clinical significance in tumor progression and prognosis remains unclear. We explored the association between STON2 and the clinicopathological characteristics of epithelial ovarian cancer (EOC). The STON2 levels in ovarian cancer and normal cell lines and tissues were detected by real-time PCR and Western blot analyses. STON2 protein expression was also detected by an immunohistochemical analysis. The clinical significance of STON2 expression in ovarian cancer was statistically analyzed. STON2 significantly increased in the ovarian cancer cell lines and tissues compared to the normal ones. In the 89 EOC samples tested, STON2 expression was significantly correlated with intraperitoneal metastasis, intestinal metastasis, intraperitoneal recurrence, ascites containing tumor cells, and CA153 level. Moreover, patients with STON2 protein overexpression were more likely to exhibit platinum resistance and to have undergone neoadjuvant chemotherapy. Patients with high STON2 protein expression had a tendency to have a shorter overall survival and a poor prognosis. A multivariate analysis showed that STON2 was an independent prognostic predictor for EOC patients. In conclusion, STON2 plays an important role in the progression and prognosis of ovarian carcinoma, especially in platinum resistance, intraperitoneal metastasis, and recurrence. STON2 can be a novel antitumor drug target and biomarker which predicts an unfavorable prognosis for EOC patients.

Upregulation of centrosomal protein 55 is associated with unfavorable prognosis and tumor invasion in epithelial ovarian carcinoma.

Centrosomal protein 55 (CEP55) is a cell cycle regulator implicated in development of certain cancers. However, characteristics of CEP55 expression and its clinical/prognostic significance are unclear in human epithelial ovarian carcinoma (EOC). Therefore, we investigated the expression and clinicopathological significance of CEP55 in patients with EOC and its role in regulating invasion and metastasis of ovarian cell lines. CEP55 mRNA and protein expression levels were detected by quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry (IHC). Potential associations of CEP55 expression scores with clinical parameters and patient survival were evaluated. CEP55 function was investigated further using RNA interference, wound healing assay, transwell assay, immunofluorescence analysis, qRT-PCR, and Western blotting. CEP55 was significantly upregulated in ovarian cancer cell lines and lesions compared with normal cells and adjacent noncancerous ovarian tissues. In the 213 EOC samples, CEP55 protein levels were positively correlated with clinical stage (P < 0.001), lymph node metastasis (P < 0.001), intraperitoneal metastasis (P < 0.001), tumor recurrence (P < 0.001), differentiation grade (P < 0.001), residual tumor size (P < 0.001), ascites see tumor cells (P = 0.020), and serum CA153 level (P < 0.001). Moreover, patients with aberrant CEP55 protein expression showed tendencies to receive neoadjuvant chemotherapy (P < 0.001) and cytoreductive surgery (P = 0.020). By contrast, no significant correlation was detected between the protein levels and patient age, histological type, or serum CA125, CA199, CA724, NSE, CEA, and ß-HCG levels. Patients with high CEP55 protein expression had shorter overall survival and disease-free survival compared with those with low CEP55 expression. Multivariate analysis implicated CEP55 as an independent prognostic indicator for EOC patients. Additionally, downregulation of CEP55 in ovarian cancer cells remarkably inhibited cellular motility and invasion. Aberrant CEP55 expression may predict unfavorable clinical outcomes in EOC patients and play an important role in regulating invasion in ovarian cancer cells. Thus, CEP55 may serve as a prognostic marker and therapeutic target for EOC.

C14ORF166 overexpression is associated with pelvic lymph node metastasis and poor prognosis in uterine cervical cancer.

C14ORF166 (chromosome 14 open reading frame 166) is a transcriptional repressor related to the regulation of centrosome architecture. However, the role of C14ORF166 in the development and progression of cancer remains largely unknown. The aim of this study was to investigate the expression and clinicopathological significance of C14ORF166 in cervical cancer. C14ORF166 expression was analyzed using quantitative real-time PCR (RT-PCR) and Western blotting in cervical cancer cell lines and eight paired cervical cancer samples and the adjacent normal tissues. Immunohistochemistry was used to analyze C14ORF166 protein expression in 148 clinicopathologically characterized cervical cancer specimens. Statistical analyses were performed to evaluate the relationship between the expression of C14ORF166 and clinicopathologic features and prognosis. C14ORF166 mRNA and protein expression were significantly upregulated in cervical cancer cell lines and tissue samples (P < 0.05). Immunohistochemical analysis revealed a high expression of C14ORF166 was observed in 39.9 % (59/148) of the cervical cancer specimens; the remaining samples expressed low levels or did not express any detectable C14ORF166. The chi-square test indicated that high-level expression of C14ORF166 was significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001), vital status (P = 0.026), tumor size (P = 0.034), serum squamous cell carcinoma antigen level (SCC-Ag; P = 0.035), and pelvic lymph node metastasis (P < 0.001). Patients with highly expressed C14ORF166 showed a tendency to receive postoperative chemotherapy (P = 0.005) and postoperative radiation (P = 0.008). Furthermore, high C14ORF166 expression was associated with poorer overall survival compared to low C14ORF166 expression, and C14ORF166 was a significant prognostic factor in univariate and multivariate analysis (P < 0.05). High C14ORF166 expression had prognostic value for poor outcome in cervical cancer. C14ORF166 may represent a biomarker of pelvic lymph node metastasis and enable the identification of high-risk patients along with selection of appropriate treatment strategies.

NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer.

BACKGROUND: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. METHODS: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC). NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. RESULTS: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.006), squamous cell carcinoma antigen (p = 0.006), vital status (p < 0.001), tumor recurrence (p = 0.001), chemotherapy (p = 0.039), and lymph node metastasis (p < 0.001). Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. CONCLUSIONS: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer.

[Automatic Field Calibration and Analysis of Satellite Based on Hyper-Spectral Ratio Radiometer].

With the demand of calibration technology of high frequency and high precision in terms of the optical remote sensing satellite of China, and the deficiency of the artificial work, the automatic system of hyper-spectral ratio radiometer was developed by investigation the calibration situation of domestic and abroad satellite, then the automatic calibration of satellite sensor was carried out. According to the parameters demand of field calibration and the goal of automation, the ratio radiometer was designed to measure global spectral irradiance by integrating sphere, and the diffuse spectral irradiance was measure by the shelter, so the diffuse-global ratio was calculated by these data. Simultaneity the ground radiation was measured with radiometer optical-lens and the automatic observation of atmospheric and surface radiation characteristics was achieved, In addition, the data pre-processing of real-time and remote transmission were integrated in the system. With the field test on the Dunhuang radiometric calibration sites in 2015, the radiometer worked in an ideal way, and the atmospheric optical parameters and surface reflectance data were acquired, which support the calibration of satellite sensor. The comparison with the traditional measurement was carried, the relative deviation of the surface reflectance is less than 5%, and the absolute deviation of the atmospheric parameters is less than 5% and the diffuse ratio is less than 0.015%. According to the measured data and based on irradiance-based method, the field calibration applied to the band 1~5 of Aqua MODIS, the relative deviation of band 1~4 is less than 1% while the band 57.24%, so the requirement of the automatic calibration of the satellite sensor was satisfied preliminarily.

Putative stem cell markers in cervical squamous cell carcinoma are correlated with poor clinical outcome.

BACKGROUND: The aim of this study was to elucidate the value of putative cancer stem cell markers Musashi-1, ALDH1, Sox2, and CD49f in predicting the prognosis in cervical squamous cell carcinoma (CSCC). METHODS: Real-time PCR and immunohistochemistry staining was performed to examine Musashi-1, ALDH1, Sox2, and CD49f expression in archived specimens of CSCC patients with postoperative chemotherapy. Kaplan-Meier analysis and Cox proportional hazards model were used to assess the prognostic impact of CSC markers for overall survival (OS) and recurrent-free survival (RFS). RESULTS: The Real-time PCR data showed that the expression of all markers were increased in CSCC tissues compared with in paired normal cervical tissues (P < 0.05). The IHC result showed that high expression of Msi1, ALDH1, Sox2, and CD49f was found in 25.7%, 43.0%, 62.0% and 29.0% CSCC samples, respectively. Moreover, high expression of Msi1 (P = 0.033 and P = 0.003, respectively), ALDH1 (P = 0.015 and P = 0.002, respectively), and Sox2 (P = 0.005 and P = 0.003, respectively), and low expression of CD49f (P = 0.027 and P = 0.025, respectively) were correlated with poor OS and PFS in CSCC patients. Interestingly, tumors with Msi1(high)/CD49f(low) expression had the poorest prognosis according to Msi1/CD49f stratification. In multivariate Cox regression analysis, Sox2 expression (P = 0.047 and P = 0.018, respectively), ALDH1 expression (P = 0.013 and P = 0.003, respectively), and CD49f expression (P = 0.008 and P = 0.003, respectively) were independent prognostic markers for both OS and RFS. CONCLUSIONS: Our results suggest that cancer stem cell markers are linked with poor prognosis of CSCC patients.

Establishment of the retroperitoneal lymph node metastasis model of endometrial VX2 carcinoma in rabbits and observation of its metastatic features.

BACKGROUND: The objective of this study is to establish the retroperitoneal lymph node metastasis model of endometrial VX2 carcinoma in rabbits and observe of its metastatic features. METHODS: The VX2 cells were transplanted into the uterine muscularis mucosae of 48 rabbits by injecting carcinoma mass suspension. According to time, the rabbits were killed after the transplantation of VX2 cells, and they were divided into six groups, 15-, 18-, 21-, 24-, 27-, and 30-day group, and six rabbits in each group. Control groups consisted of those receiving no treatment or an injection of saline. The specimens of transplanted endometrial carcinoma and retroperitoneal lymph node in the rabbits were examined histopathologically after they were killed. RESULTS: All rabbits developed VX2 endometrial carcinoma which was confirmed with pathological examination. Significantly increased tumor volume was observed at day 24, 27, and 30 post-injection of VX2 cells (P < 0.05). The retroperitoneal lymph nodes were not enlarged completely in each rabbit in the 15-day group, partly enlarged in the 18- and 21-day group, and all enlarged in the 24-, 27-, and 30-day group. The histopathological examination revealed no complete retroperitoneal lymph node metastasis in the 15- and 18-day group, partial metastasis in the 21-day group, and complete metastasis in the 24-, 27-, and 30-day group. CONCLUSIONS: The model was established successfully by injecting carcinoma mass suspension, and various retroperitoneal lymph node metastasis model of endometrial VX2 carcinoma can be established rapidly in a month after the transplantation.

[A novel method of multi-channel feature extraction combining multivariate autoregression and multiple-linear principal component analysis].

Brain-computer interface (BCI) systems identify brain signals through extracting features from them. In view of the limitations of the autoregressive model feature extraction method and the traditional principal component analysis to deal with the multichannel signals, this paper presents a multichannel feature extraction method that multivariate autoregressive (MVAR) model combined with the multiple-linear principal component analysis (MPCA), and used for magnetoencephalography (MEG) signals and electroencephalograph (EEG) signals recognition. Firstly, we calculated the MVAR model coefficient matrix of the MEG/EEG signals using this method, and then reduced the dimensions to a lower one, using MPCA. Finally, we recognized brain signals by Bayes Classifier. The key innovation we introduced in our investigation showed that we extended the traditional single-channel feature extraction method to the case of multi-channel one. We then carried out the experiments using the data groups of IV-III and IV - I. The experimental results proved that the method proposed in this paper was feasible.

[Spectral scanning measurement of high-precision solar irradiance-meter].

In order to measure the radiation of the sun absolutely and retrieve the characterization of the atmosphere precisely, a high-precision solar spectral irradiance meter working in 0.4-1.0 microm band was developed. A Fèry prism was employed to disperse the incident sunlight and a closed-loop control method was adopted for spectral scanning in this solar irradiance meter. The design of spectral scanning measurement was depicted in detail. The design requirements of Fèry prism were given and spectral dispersion was achieved by single element. The trap detectors were used to ensure precise spectral measurement. According to the parameters of the trap detectors, the demands and method of temperature control were introduced. The design of spectral scanning structure was introduced, and wavelengths were positioned accurately. The requirements for parameters, stability and power supply of voice coil actuator were given and the wavelength position error of 0. 025% was achieved. Spectral scanning measurement of 0.4-1.0 microm was accomplished in outdoor experiments. A comparison was carried out with visible-short wave infrared spectrometer and auto-sunphotometer (CE318). Results indicate that absorption peak locations of spectral scanning measurement of irradiance meter are correct, and the relative deviation from CE318 measurements is less than 0.13% for all day, and the relative deviation of optical depth in visible and near infrared band is less than 2% and 5%, respectively.

Trichostatin A-modified vaccine provides superior protection against ovarian cancer formation and development.

More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.